Many drugs and hormones appear to raise or lower blood pressure by altering the movements of calcium, sodium, and/or potassium ions in the vascular smooth muscle cell (VSMC). The two major goals of the laboratory are to understand how certain vasoactive hormones regulate cation transport in VSM and to examine cation homeostasis in cultured VSMC from hypertensive rat strains. Smooth muscle cells cultured from rat aorta respond to angiotensin receptor stimulation with rapid increases in cytoplasmic inositol phosphates (mono-, di-, and tri-) and calcium (measured by increases in quin2 flourescence and steady-state 45Ca2+). Additionally, angiotensin II (AII) increases Na+/H+ antiport and Na+, K+, Cl- symport and depolarizes the cell membrane. (All of these AII-evoked responses are blocked by Sarl, leu8-AII.) Beta-adrenoreceptor stimulation increases cyclic AMP and rapidly transforms the morphology of the cells. The specific aims of this project are: (1) to further define the transmembrane signaling events evoked by AII and establish the cause-effect relationships among the various responses to AII; (2) to identify the sequence of biochemical events by which beta-adrenoreceptor stimulation alters calcium exchange and rounds cultured VSM cells; (3) to test the role of hormone-evoked polyphosphoinositide hydrolysis, increased cytoplasmic Ca2+ activity, and increased Na+/H+ antiport and Na+, K+, Cl- symport on the growth of cultured VSM cells; (4) to culture VSMC from hypertensive rat strains; (5) to compare basal and hormone-perturbed cation homeostasis (including cytoplasmic calcium activity) and growth control by basoactive hormones in the VSMC from the normotensive and hypertensive strains. The latter investigations provide a novel test of the hypothesis that a membrane defect in cation transport in the SMC is a primary factor in the etiology of genetic hypertension and offer the possibility of establishing cell lines for identifying the genetic lesions which predispose the organism to hypertension.